Abstract
Hypoxic exposure results in several pathophysiological conditions associated with nervous system, these include acute and chronic mountain sickness, loss of memory, and high altitude cerebral edema. Previous reports have also suggested the role of hypoxia in pathogenesis of depression and related psychological conditions. On the other hand, sub lethal intermittent hypoxic exposure induces protection against future lethal hypoxia and may have beneficial effect. Therefore, the present study was designed to explore the neuroprotective role of intermittent hypobaric hypoxia (IHH) in Unpredictable Chronic Mild Stress (UCMS) induced depression like behaviour in rats. The IHH refers to the periodic exposures to hypoxic conditions interrupted by the normoxic or lesser hypoxic conditions. The current study examines the effect of IHH against UCMS induced depression, using elevated plus maze (EPM), open field test (OFT), force swim test (FST), as behavioural paradigm and related histological and molecular approaches. The data indicated the UCMS induced depression like behaviour as evident from decreased exploration activity in OFT with increased anxiety levels in EPM, and increased immobility time in the FST; whereas on providing the IHH (5000m altitude, 4hrs/day for two weeks) these behavioural changes were ameliorated. The morphological and molecular studies also validated the neuroprotective effect of IHH against UCMS induced neuronal loss and decreased neurogenesis. Here, we also explored the role of Brain-Derived Neurotrophic Factor (BDNF) in anticipatory action of IHH against detrimental effect of UCMS as upon blocking of BDNF-TrkB signalling the beneficial effect of IHH was nullified. Taken together, the findings of our study demonstrate that the intermittent hypoxia has a therapeutic potential similar to an antidepressant in animal model of depression and could be developed as a preventive therapeutic option against this pathophysiological state.
Highlights
In humans, the development of different psychological conditions has been vividly influenced by the chronic exposure to stressful environment
Out of six groups three groups kept in control conditions with Intermittent hypobaric hypoxia (IHH) or antidepressant treatment (Imipramine) and other three groups were exposed to Unpredictable Chronic Mild Stress (UCMS) with Intermittent hypobaric hypoxia (IHH) or antidepressant treatment (Imipramine) as shown in Table 1 and Fig 1
Results showed that intermittent hypobaric hypoxia (IHH) do not cause cell loss as no change in neuronal densities was found in hippocampus in group exposed to IHH as compared to control
Summary
The development of different psychological conditions has been vividly influenced by the chronic exposure to stressful environment. IH can be beneficial to both human beings and animals Both preconditioning and IH as reported earlier, exerts an endogenous protective mechanism that helps neurons survive further lethal insults. The acute and the chronic stress treatments have been reported to decrease brain derived neurotrophic factor (BDNF) mRNA levels throughout the hippocampus [10, 18, 19]. Acute and chronic stress have been known to decrease the levels of BDNF in DG and hippocampus [23]. Antidepressant treatment increases the expression of BDNF in these regions [24], and can prevent the stress induced decrease in BDNF levels. The present study is designed to explore the effect of IHH on depression like behaviour using unpredictable chronic mild stress induced depression as a model. The potential mechanisms underlying UCMS induced modulation of BDNF expression in hippocampus was studied
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